Excess Lipids Keep Dengue at Bay

The Aedes aegypti mosquito can transmit dengue virus; however, infection with endosymbiotic bacteria from the Wolbachia genus reduces viral transmission from these insects. Consequently, Wolbachia-infected mosquitos are one biocontrol agent used in areas with endemic dengue cases. 

“We are trying to go backwards now, because the intervention works, but we don’t know how,” said Robson Loterio, a microbiologist at the Burnet Institute and author of a paper published in mBio exploring the mechanism of Wolbachia’s antiviral activity.¹ The findings can help researchers prevent viral escape from this biocontrol method. 

Loterio and his team infected A. aegypti cells with antiviral Wolbachia strains. Using transmission electron microscopy and confocal microscopy, they showed that these bacteria predominantly clustered at the cell’s endoplasmic reticulum (ER). 

The ER produces molecules used in lipid droplet synthesis. Since both Wolbachia and dengue rely on lipid metabolism, the team investigated the effect of Wolbachia on droplet formation during viral infection by comparing antiviral Wolbachia-infected cells to Wolbachia-free cells.² Lipid droplets accumulated in both types of cells, but cells with the bacteria had more lipid accumulation. 

Next, the team explored whether altered lipid droplet production influenced dengue virus replication by treating antiviral Wolbachia-infected and Wolbachia-free cells with an inhibitor to fatty acid synthase, an enzyme involved in lipid droplet production. The inhibitor decreased the amount of lipid droplets in both conditions. However, while this impaired dengue virus replication in Wolbachia-free cells, it enabled viral replication in antiviral Wolbachia-infected cells, supporting the role of excess lipid droplet formation in Wolbachia's antiviral activity. 

Matthew Aliota, a virologist at the University of Minnesota who was not affiliated with the study, pointed out that the study was predominantly based on cell culture work, but added that it was still a good start to understand this mechanism. “It just builds on what is known about Wolbachia pathogen blocking, in the sense that it's very complex.”